Showing papers by "Sven Mahner published in 2023"
TL;DR: More than 20 ADC formulations are in clinical trials for the treatment of ovarian, cervical and endometrial tumors as mentioned in this paper , and a review summarizes key evidence supporting their use and therapeutic indications including results from late-stage development trials investigating MIRV in ovarian cancer and TV in cervical cancer.
Abstract: The clinical development of antibody drug conjugates (ADCs) in ovarian cancer began in 2008 with farletuzumab, a humanized monoclonal antibody, and vintafolide, an antigen drug conjugate, both targeting alpha folate receptor. Over the years, this novel class of drugs expanded to agents with a more sophisticated design and structure, targeting tissue factor (TF) in cervical cancer or human epidermal growth factor receptor 2 (HER2) in endometrial cancer. Despite the impressive number of patients included in clinical trials investigating different ADCs across gynecological cancers, it was only recently that the Food and Drug Administration (FDA) granted accelerated approvals to the first ADCs in gynecologic cancer. In September 2021, the FDA approved tisotumab vedotin (TV) in recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. This was followed in November 2022, by the approval of mirvetuximab soravtansine (MIRV) for adult patients with folate receptor alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Currently, the field of ADCs is rapidly expanding and more than 20 ADC formulations are in clinical trials for the treatment of ovarian, cervical and endometrial tumors. This review summarizes key evidence supporting their use and therapeutic indications, including results from late-stage development trials investigating MIRV in ovarian cancer and TV in cervical cancer. We also outline new concepts in the field of ADCs, including promising targets such as NaPi2 and novel drug delivery platforms such as dolaflexin with a scaffold-linker. Finally, we briefly present challenges in the clinical management of ADC toxicities and the emerging role of ADC combination therapies, including chemotherapy, anti-angiogenic and immunotherapeutic agents.
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TL;DR: The role of progesterone receptor A (PRA) for the survival outcome of cervical cancer patients is ambiguous as mentioned in this paper , however, it has been shown that PRA plays a rather protective role in cancer development.
Abstract: The role of progesterone receptor A (PRA) for the survival outcome of cervical cancer patients is ambiguous. In mouse models, it has been shown that PRA plays a rather protective role in cancer development. The aim of this study was to assess its expression by immunohistochemistry in 250 cervical cancer tissue samples and to correlate the results with clinicopathological parameters including patient survival. PRA expression was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) classification scores. PRA was significantly overexpressed in adenocarcinomas compared to squamous epithelial carcinoma subtypes. Correlation analyses revealed a trend association with the HPV virus protein E6, a negative correlation with p16 and a positive correlation with EP3. PRA expression was also associated with the expression of RIP140, a transcriptional coregulator that we previously identified as a negative prognostic factor for survival in cervical cancer patients. Univariate survival analyses revealed PRA as a negative prognosticator for survival in patients with cervical adenocarcinoma. Multivariate analyses showed that simultaneous expression of RIP140 and PRA was associated with the worst survival, whereas with negative RIP140, PRA expression alone was associated with the best survival. We can therefore assume that the effect of nuclear PRA on overall survival is dependent upon nuclear RIP140 expression.
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TL;DR: In this article , the authors concluded that HIPEC should remain within the remit of clinical trials for epithelial ovarian cancer (EOC) patients, with however contradicting results and several quality aspects that made the interpretation of their findings critical.
Abstract: An international joint statement about the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer was published in 2016, warning about the uncritical use of HIPEC outside controlled studies. This statement has now been updated after the most recent literature was reviewed by the participating study groups and societies. HIPEC became a treatment option in patients with advanced colon cancer after positive results of a randomized trial comparing surgery and HIPEC versus palliative treatment alone. Although this trial did not compare the added value of HIPEC to surgery alone, HIPEC for the treatment of peritoneal metastases was in the subsequent years generalized to many other cancer types associated with peritoneal carcinomatosis including epithelial ovarian cancer (EOC). In the meantime, new evidence from prospective randomized trials specifically for EOC-patients emerged, with however contradicting results and several quality aspects that made the interpretation of their findings critical. Moreover, three additional trials in colorectal cancer failed to confirm the previously presumed survival benefit through the implementation of HIPEC in peritoneally disseminated colorectal cancers. Based on a still unclear and inconsistent landscape, the authors conclude that HIPEC should remain within the remit of clinical trials for EOC-patients. Available evidence is not yet sufficient to justify its broad endorsement into the routine clinical practice.
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TL;DR: In this article , the authors conducted an anonymous cross-sectional survey online among N = 2463 adults living in Germany and assessed individuals' desire for parenthood during the COVID-19 pandemic.
Abstract: The COVID-19 pandemic continues to spread across the globe and is associated with significant clinical and humanitarian burden. The desire for parenthood has been described to be positively correlated with psychological well-being: An unfulfilled wish for parenthood is associated with impaired mental health, and the wish for parenthood is a predictor for the development of depressive symptoms. While higher rates of anxiety and depression have been reported in individuals with minoritized sexual identities (compared to heterosexual individuals) during the COVID-19 pandemic, the specific impact of the pandemic and its social restriction measures on this population is poorly understood.From April to July 2020, we conducted an anonymous cross-sectional survey online among N = 2463 adults living in Germany. We screened for depressive symptoms (Patient Health Questionnaire-4; PHQ-4) and assessed individuals' desire for parenthood during the pandemic, and motives for or against the desire for parenthood (Leipzig questionnaire on motives for having a child, Version 20; LKM-20), with the aim of identifying differences between individuals with minoritized sexual identities and heterosexual individuals.Compared to heterosexual individuals (n = 1304), individuals with minoritized sexual identities (n = 831) indicated higher levels of depressive symptoms. In our study sample the majority of all participants (81.9%) reported no change in the desire for parenthood since the COVID-19 pandemic.The findings underline the unmet need for social, psychological and medical support in regard to family-planning and the desire for parenthood during a pandemic. Furthermore, future research should explore COVID-19-related psychological consequences on individuals' desire for parenthood and building a family.
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TL;DR: The 12th International Charité Mayo Conference as discussed by the authors was held in Berlin, Germany from 26-29 April, 2023, with the theme of "GLOBAL PERSPECTIVES and Future Directions".
Abstract: s of the 12th International Charité Mayo Conference, 26-29 April, 2023, Berlin, Germany ABSTRACTS OF THE 12th INTERNATIONALS OF THE 12th INTERNATIONAL CHARITÉ MAYO CONFERENCE ON “GLOBAL PERSPECTIVES AND FUTURE DIRECTIONS
TL;DR: In this article , a study untersucht die Expression of Galektin-10 in Plazenten von Müttern mit Gestationsdiabetes mellitus (GDM) and unterstütze die Expression in Platzenten mit GDM.
Abstract: Einleitung Galektine spielen eine wichtige Rolle bei immunregulatorischen Prozessen und Autoimmunerkrankungen [1] [2]. Galektin-10 ist ein cytoplasmatisches Protein, welches in humanen Eosinophilen vorkommt und in eine Vielzahl von eosinophilen-vermittelten Erkrankungen involviert ist [3] [4]. Vorhergehende Studien konnten einen Zusammenhang zwischen dem Expressionsmuster von Galektinen und dem Auftreten von schwangerschaftsassoziierten Pathologien wie der Präeklampsie, dem HELLP-Syndrom und Gestationsdiabetes mellitus (GDM) identifizieren [5] [6]. Diese Studie untersucht die Expression von Galektin-10 in Plazenten von Müttern mit GDM.
TL;DR: The European Society of Gynaecological Oncology (ESGO) as mentioned in this paper published a set of guidelines for the management of patients with vulvar cancer based on the new evidence.
Abstract: Background As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer. Objective To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer. Methods The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe). To ensure that the statements were evidence-based, new data identified from a systematic search were reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 206 international practitioners in cancer care delivery and patient representatives. Results The updated guidelines cover comprehensively diagnosis and referral, staging, pathology, pre-operative investigations, surgical management (local treatment, groin treatment, sentinel lymph node procedure, reconstructive surgery), (chemo)radiotherapy, systemic treatment, treatment of recurrent disease (vulvar, inguinal, pelvic, and distant recurrences), and follow-up. Management algorithms are also defined.
TL;DR: In this paper , the expression of the nuclear co-repressor NCOR2 was evaluated by immunohistochemistry in a cohort of 156 epithelial ovarian cancer (EOC) tumor samples and correlated with GPER expression.
Abstract: The significance of the non-classical G-protein-coupled estrogen receptor (GPER) as positive or negative prognostic factor for ovarian cancer patients remains still controversial. Recent results indicate that an imbalance of both co-factors and co-repressors of nuclear receptors regulates ovarian carcinogenesis by altering the transcriptional activity through chromatin remodeling. The present study aims to investigate whether the expression of the nuclear co-repressor NCOR2 plays a role in GPER signaling which thereby could positively impact overall survival rates of ovarian cancer patients.NCOR2 expression was evaluated by immunohistochemistry in a cohort of 156 epithelial ovarian cancer (EOC) tumor samples and correlated with GPER expression. The correlation and differences in clinical and histopathological variables as well as their effect on prognosis were analyzed by Spearman's correlation, Kruskal-Wallis test and Kaplan-Meier estimates.Histologic subtypes were associated with different NCOR2 expression patterns. More specifically, serous and mucinous EOC demonstrated a higher NCOR2 expression (P = 0.008). In addition, high nuclear NCOR2 expression correlated significantly with high GPER expression (cc = 0.245, P = 0.008). A combined evaluation of both high NCOR2 (IRS > 6) and high GPER (IRS > 8) expression revealed an association of a significantly improved overall survival (median OS 50.9 versus 105.1 months, P = 0.048).Our results support the hypothesis that nuclear co-repressors such as NCOR2 may influence the transcription of target genes in EOC such as GPER. Understanding the role of nuclear co-repressors on signaling pathways will allow a better understanding of the factors involved in prognosis and clinical outcome of EOC patients.
TL;DR: In this article , the potential prognostic impact of anastomotic leakage following bowel resection was analyzed by Kaplan-Meier method and log-rank tests regarding progression-free (PFS) and overall survival (OS).
Abstract: 5566 Background: Anastomotic leakage (AL) is an important and severe complication following bowel resection in cytoreductive surgery (CRS) for ovarian cancer (OC). Identifying patients (pts) at risk for AL could improve clinical management and reduce frequency and severity of complications. Methods: AGO-OVAR.OP3/LION intraoperatively randomized 647 pts with advanced OC (FIGO IIB-IV) following complete cytoreduction with unsuspicious lymph nodes to either undergo systematic pelvic and paraaortic lymphadenectomy (LNE) or not. All pts who underwent bowel resection were included in this analysis. Potential prognostic impact of AL was analyzed by Kaplan-Meier method and log-rank tests regarding progression-free (PFS) and overall survival (OS). Risk factors for AL in a subset of clinicopathological parameters were evaluated by calculating odds ratio (OR) with 95% confidence interval (CI) in univariate and multivariate logistic regression models. A stepwise variable selection algorithm using the Akaike Information Criteria (AIC) for identification of the final logistic regression model was applied. P values presented were two-tailed, and P<0.05 was considered as statistically significant. Results: Among all 647 randomized pts, AL was noted in 24 (3.7 %) pts. The AL rate of the 336 pts with bowel surgery during CRS (median age 61.3 years; 316 large bowel, 94 small bowel resections) was 7.1% (24/336 pts). Pts following stoma formation had an AL rate of 5.5% (3/55 pts) compared to 7.5% (21/281 pts) in pts without stoma. Median PFS was 18 months in pts with AL versus 19 months in the no-AL-group (hazard ratio (HR) 0.86; 95% CI 0.5 to 1.4, P=0.53), median OS was 31 months in the AL group and 58 months in the no-AL-group (HR 0.69; 95% CI 0.4 to 1.2, P=0.17). The clinicopathological characteristics “volume of blood loss” (OR 1.05 per 100cc; 95% CI 1.01-1.10) and “LNE vs non-LNE” (OR 4.10; 95% CI 1.60-12.62) were identified as factors potentially predictive for AL in univariate analysis, and both factors (volume of blood loss [OR 1.04 per 100cc, 95% CI 1.0001-1.09], LNE vs non-LNE [OR 3.67, 95% CI 1.41-11.39]) remained a significant independent factor in multivariate analysis. Conclusions: Considering the high surgical complexity in this large prospective surgical trial, the overall rate of AL following bowel surgery was relatively low and had no significant impact on PFS or OS. While protective stoma formation was not identified as protective factor in this cohort, volume of blood loss and LNE procedure were clinical parameters associated with higher risk of AL. Being potential surrogates for extensive surgery, these factors should be considered in perioperative management in pts with advanced OC. Further specific factors predicting AL were not identified. Clinical trial information: NCT00712218 .
TL;DR: In this article , the expression of IL-6 and GRO-alpha as well as the infiltration of macrophages in the placenta of obese, non-diabetic pregnancies was examined by immunohistochemistry.
TL;DR: In this paper , the authors used an in vitro model to investigate whether sLeX and LeY are playing a role in the embryo implantation process mediated by IL-1β.
Abstract: Abstract Cell surface carbohydrate antigens sialyl Lewis X (sLeX) and Lewis Y (LeY) are paramount glycoconjugates and are abundantly expressed in the receptive endometrium. Furthermore, among the important biological functions of both antigens is their role in leukocytes adhesion and extravasation. Interleukin-1 beta (IL-1β) is involved in the process of human embryo implantation and placenta development. Here, we used an in vitro model to investigate whether sLeX and LeY are playing a role in the embryo implantation process mediated by IL-1β. Our results are showing that the expression of cell surface sLeX was enhanced in endometrial RL95-2 cells after exposure to IL-1β. RT-qPCR detection indicated that the transcript level of glycosyltransferase gene fucosyltransferase 3 (FUT3) was significantly elevated and that of FUT4/7 and ST3 beta-galactoside alpha-2,3-sialyltransferase 3/4 (ST3GAL3/4) were decreased by treatment with IL-1β. Modulatory role of glycosyltransferase FUT3 on sLeX biosynthesis was determined by FUT3 siRNA transfection in RL95-2 cells. Results showed that the expression level of sLeX was suppressed, but no change was observed in regard to LeY. Moreover, IL-1β promoted the HTR-8/SVneo trophoblast spheroids attachment to the RL95-2 endometrial monolayer, which was partially blocked by anti-sLeX antibody and FUT3 knockdown. Gene expression analysis of the RNA-seq transcriptome data from human secretory endometrium demonstrated a significantly higher level of FUT3 in the mid-secretory phase compared to the early secretory phase, which was correlated with the expression of IL1B. In summary, the inflammatory microenvironment at the fetomaternal interface can regulate the glycosylation pattern of endometrial cells at the time of implantation. SLeX can be significantly induced by IL-1β via increasing FUT3 expression, which facilitates the trophoblast adhesion during embryo implantation. Summary Sentence sLeX can be significantly induced by IL-1β via increasing FUT3 expression, which facilitates trophoblast adhesion during human embryo implantation. Graphical Abstract
TL;DR: Developing clinically relevant and evidence-based guidelines to improve the quality of care for women with gynecologic cancers across Europe based on the best available evidence and expert agreement is published.
Abstract: Background As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer. Objective To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer. Methods The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe). To ensure that the statements were evidence-based, new data identified from a systematic search were reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 206 international practitioners in cancer care delivery and patient representatives. Results The updated guidelines cover comprehensively diagnosis and referral, staging, pathology, pre-operative investigations, surgical management (local treatment, groin treatment, sentinel lymph node procedure, reconstructive surgery), (chemo)radiotherapy, systemic treatment, treatment of recurrent disease (vulvar, inguinal, pelvic, and distant recurrences), and follow-up. Management algorithms are also defined.
TL;DR: In this article , a review summarizes the current indications for PARPi, including their role in recurrent and first-line maintenance treatment for advanced ovarian cancer, and highlights the patient groups most likely to benefit from each of the three different PARPi.
Abstract: The past 5 years have seen several fundamental advances in ovarian cancer, with important new insights towards novel therapeutic opportunities within the DNA repair pathway. With the incorporation of poly (ADP-ribose) polymerase inhibitors (PARPi) into maintenance treatment regimens, the management of short- and long-term adverse events are key clinical priorities. Currently, three different PARPi are clinically beneficial and have been approved for primary and recurrent ovarian cancer: olaparib, niraparib, and rucaparib. The duration of treatment with PARPi in patients with ovarian cancer varies; patients can receive treatment for up to 2 or 3 years in first-line setting, or continue treatment until unacceptable toxicity or progression occurs in recurrent disease. Despite their similar mechanisms of action, these three inhibitors have specific toxicity profiles, which may lead to dose interruptions or discontinuation of treatment. This review summarizes the current indications for PARPi, including their role in recurrent and first-line maintenance treatment for advanced ovarian cancer. We also outline dose modifications leading to treatment disruption and potential changes in quality of life after prolonged treatment. Finally, we highlight the patient groups most likely to benefit from each of the three different PARPi.
TL;DR: In this paper , a review summarizes recent findings on the cellular origin of placental macrophages, and provides a comprehensive description of their phenotypes, corresponding molecular markers and functions in human placenta.
TL;DR: In this article , aktuellen Entwicklungen und ein Ausblick auf weitere Therapieoptionen werden im Beitrag zusammengefasst.
Abstract: Sowohl beim Endometrium- als auch beim Zervixkarzinom hat sich das therapeutische Management im klinischen Alltag in den vergangenen Jahren entscheidend verändert. Neben der Berücksichtigung von molekularen Charakteristika in der Routine der pathologischen Diagnostik ist die Immuntherapie nun als Standard-Therapieoption in verschiedenen Therapielinien etabliert, was durch mehrere neue Zulassungen bestätigt wurde. Beim rezidivierten Endometriumkarzinom kann, abhängig vom MMR(„mismatch repair“)-Status, eine Immuntherapie als Mono- oder als Kombinationstherapie mit dem Tyrosinkinaseinhibitor Lenvatinib eingesetzt werden. Beim metastasierten Zervixkarzinom wird die kombinierte Erstlinienchemotherapie abhängig vom PD-L1(„programmed cell death 1 ligand 1“)-Status durch Pembrolizumab ergänzt, in späteren Therapielinien kann Cemiplimab als Monotherapie eingesetzt werden. Die aktuellen Entwicklungen und ein Ausblick auf weitere Therapieoptionen werden im Beitrag zusammengefasst.
TL;DR: In this paper , the authors analyzed the impact of lockdown measures on preterm birth rates in Germany during the COVID-19 pandemic and found that less physical activity might have led to the protective effect by lockdown measures.
Abstract: Abstract Purpose After living with the COVID-19 pandemic for more than 2 years, the impact of lockdown measures on preterm birth rates is inconsistent according to data from different countries. In this study, rates of preterm-born infants during the time of COVID-19-related lockdowns were analyzed in a tertiary perinatal center at Munich University, Germany. Methods We analyzed the number of preterm births, infants, and stillbirths before 37 weeks of gestation during the German COVID-19 lockdown period compared to the same time periods in the years 2018 and 2019 combined. Additionally, we expanded the analysis to Pre- and Post-Lockdown Periods in 2020 compared to the respective control periods in the years 2018 and 2019. Results Our database shows a reduction in the rate of preterm infants during the COVID-19 lockdown period (18.6%) compared to the combined control periods in 2018 and 2019 (23.2%, p = 0.027). This was mainly based on a reduced rate of preterm multiples during the lockdown period (12.8% vs. 28.9%, p = 0.003) followed by a reversed effect showing a threefold rise in multiple births after the lockdown. In singletons, the rate of preterm births was not reduced during the lockdown. The rate of stillbirths was not affected by the lockdown measures as compared to the control period (0.9% vs. 0.7%, p = 0.750). Conclusion During the COVID-19 pandemic lockdown period, we found a reduced rate of preterm-born infants compared to a combined control period in the years 2018 and 2019 in our large tertiary University Center in Germany. Due to the predominant reduction in preterm multiples, we postulate that less physical activity might have led to the protective effect by lockdown measures.
TL;DR: In this article , aktuellen Entwicklungen und ein Ausblick auf weitere Therapieoptionen werden im Beitrag zusammengefasst.
Abstract: Sowohl beim Endometrium- als auch beim Zervixkarzinom hat sich das therapeutische Management im klinischen Alltag in den vergangenen Jahren entscheidend verändert. Neben der Berücksichtigung von molekularen Charakteristika in der Routine der pathologischen Diagnostik ist die Immuntherapie nun als Standard-Therapieoption in verschiedenen Therapielinien etabliert, was durch mehrere neue Zulassungen bestätigt wurde. Beim rezidivierten Endometriumkarzinom kann, abhängig vom MMR(„mismatch repair“)-Status, eine Immuntherapie als Mono- oder als Kombinationstherapie mit dem Tyrosinkinaseinhibitor Lenvatinib eingesetzt werden. Beim metastasierten Zervixkarzinom wird die kombinierte Erstlinienchemotherapie abhängig vom PD-L1(„programmed cell death 1 ligand 1“)-Status durch Pembrolizumab ergänzt, in späteren Therapielinien kann Cemiplimab als Monotherapie eingesetzt werden. Die aktuellen Entwicklungen und ein Ausblick auf weitere Therapieoptionen werden im Beitrag zusammengefasst.
TL;DR: Wang et al. as discussed by the authors explored the prognostic significance of krüppel like factor (KLF) in BC patients and investigated its functional roles in this malignancy.
Abstract: The therapy concepts that target several members of krüppel like factor (KLF) family have been achieved in breast cancer (BC). However, the role of KLF11 in BC remains unclear. This study explored the prognostic significance of KLF11 in BC patients and investigated its functional roles in this malignancy.Immunohistochemistry (IHC) staining of KLF11 in 298 patients' samples was performed to determine the prognostic role of the KLF11. Then the protein level was correlated to clinicopathological characteristics and survival outcomes. Afterward, the function of KLF11 was explored in vitro with siRNA-mediated loss-of-function of cell viability, proliferation, and apoptosis.From the cohort study, we found that the expression of KLF11 was positively associated with highly proliferative BC of BC. Furthermore, prognostic analysis demonstrated that KLF11 was an independent negative factor for disease-free survival (DFS) and distant-metastasis-free survival (DMFS) of BC. The KLF11-related prognostic model for DFS and DMFS showed high accuracy in predicting the 3-,5- and 10 -year survival probability of BC patients. Additionally, the knockdown of KLF11 inhibited cell viability and proliferation, as well as induced cell apoptosis in MCF7 and MDA-MB-231 cells, while only inhibited cell viability and induced cell apoptosis in SK-BR-3 cells.Our study indicated that targeting KLF11 is an interesting therapeutic concept and further research could lead to a new therapeutic improvement in BC, especially in highly aggressive molecular subtypes.
TL;DR: In this article , the authors compare two different AFE classification systems by analysing the AFE cases from two university hospitals, LMU Women's University Hospital Munich and WU Hospital Basel, and find that only three of six patients had a strong suspicion of AFE (0.015%).
Abstract: Amniotic fluid embolism (AFE) is a rare life-threatening complication in obstetrics, but the diagnosis lacks a consensual definition. The objective of this study was to compare two different AFE classification systems by analysing the AFE cases from two university hospitals.In this retrospective study, all patients with a strong suspicion of AFE between 2014 and 2021 at two university hospitals, LMU Women's University Hospital Munich, and Women's University Hospital Basel, were included. Patient records were checked for the ICD-10 code O88.1 (AFE). Diagnoses were confirmed through clinical findings and/or autopsy. The presence of the diagnostic criteria of the Society of Maternal foetal Medicine (SMFM) and the AFE Foundation (AFEF) and of a new framework by Ponzio-Klijanienko et al. from Paris, France, were checked and compared using Chi-square-test.Within our study period, 38,934 women delivered in the two hospitals. Six patients had a strong suspicion of AFE (0.015%). Only three of six patients (50%) presented with all the four diagnostic criteria of the SMFM/AFEF framework. All six patients met the criteria of the modified "Paris AFE framework".Using the "Paris AFE framework" based exclusively on clinical criteria can help clinicians to diagnose AFE, anticipate the life-threatening condition of the patient and prepare immediately for best clinical care.
TL;DR: Einleitung Aktive Kommunikation mit ambulanten onkologischen PatientInnen während akuter COVID-19-Infektion and häuslicher Quarantäne zu Therapie-and Symptommanagement ist entscheidend für den COVID19- and also für the weiteren onkologicischen Therapieverlauf as discussed by the authors .
Abstract: Einleitung Aktive Kommunikation mit ambulanten onkologischen PatientInnen während akuter COVID-19-Infektion und häuslicher Quarantäne zu Therapie- und Symptommanagement ist entscheidend für den COVID-19- und auch für den weiteren onkologischen Therapieverlauf. Onkologische PatientInnen sind nach wie vor der Gefahr eines schweren COVID-19-Verlaufes ausgesetzt.
TL;DR: In this article , the Polarisationszustand der fetalen and mütterlichen Makrophagen, die sowohl bei gesunden als auch bei schwangerschaftsassoziierten Erkrankungen eine Rolle spielen, sind begrenzt.
Abstract: Einleitung Die Immunzellen der Plazenta spielen eine sehr wichtige Rolle für eine erfolgreiche Plazentation und die Vermeidung von Schwangerschaftskomplikationen. Makrophagen dominieren in Anzahl und Bedeutung sowohl im mütterlichen als auch im fetalen Teil der Plazenta. Die Erkenntnisse über den Polarisationszustand der fetalen und mütterlichen Makrophagen, die sowohl bei gesunden als auch bei schwangerschaftsassoziierten Erkrankungen eine Rolle spielen, sind begrenzt. Bislang gibt es keine repräsentative standardisierte Isolierungsmethode für den direkten Vergleich von mütterlichen und fetalen Makrophagen.
TL;DR: In this paper , the combination of pazopanib and weekly topotecan is feasible, resulting in a manageable haematological and liver toxicity, but despite its encouraging response rate, was not associated with a significant survival benefit.
Abstract: Abstract Purpose Pazopanib has promising antiangiogenetic activity in solid cancers. The investigator-initiated phase I/II trial evaluated the combination of Topotecan with Pazopanib in platinum-resistant or intermediate-sensitive recurrent ovarian cancer (ROC). Methods Patients (≥ 18 years) with first or second recurrence were enrolled in this multicentre open-label trial. Phase I analysed Topotecan 4 mg/m 2 (day 1, 8, 15, ever 28 days) for six cycles to identify the maximum tolerated dose (MTD) of Pazopanib added in a dose-escalating scheme with 400 mg starting dose. The phase II analysed safety and efficacy aspects. For all patients with clinical remission a maintenance with Pazopanib until progression was allowed. This trial is registered with ClinicalTrials.gov, number NCT 01600573. Results Between June 2012 and February 2017, 11 patients were enrolled in the phase I, and 50 patients in the phase II study. The MTD of Pazopanib was determined by 400 mg/daily. Haematological and liver toxicities determined the dose limiting toxicities (DLT) and the most common grade 3–4 adverse events: leucopenia (25%), neutropenia (22%), thrombocytopenia (19%), accumulation of cholestatic (20%) and hepatocellular damage (15%), which often caused dose modifications, but no new life-threatening events. Overall response was 16% and clinical benefit rate 68%. Median progression-free survival (PFS) was 3.5 months (95% CI 2.0—5.0). Due to early progression only 20% of the patients were able to start with maintenance treatment. Conclusion The combination of pazopanib and weekly topotecan is feasible, resulting in a manageable haematological and liver toxicity, but despite its encouraging response rate, was not associated with a significant survival benefit.
TL;DR: In this paper , the ICI-Kombination aus dem PD-1-Inhibitor Nivolumab with dem CTLA-4-inhibitor Ipilimumab was studied.
Abstract: Einleitung Der Einsatz von Immuncheckpoint-Inhibitoren (ICI) hat bisherige Therapiekonzepte gynäkologischer Tumoren drastisch gewandelt [1]. Durch Blockade wichtiger Signalwege des Immunsystems bilden tumorspezifische zytotoxische T-Lymphozyten womöglich ein immunologisches Gedächtnis aus, das zu teilweise lang andauernden Remissionsraten solider Tumore geführt hat. Unabhängig von molekularen Eigenschaften, wie der PD-L1 Expression zeigte die ICI-Kombination aus dem PD-1-Inhibitor Nivolumab mit dem CTLA-4-Inhibitor Ipilimumab nach den bisherigen Ergebnissen der Phase-I/II-Studie CheckMate 358 eine außergewöhnlich hohe Ansprechrate (medianes Gesamtüberleben 20.9 (14.4–32.8) Monate; medianes progressionsfreies Überleben 5.8 (3.8–9.3) Monate) [2], die sich auch durch den folgenden klinischen Fall darstellen lässt.
TL;DR: In this paper , a retrospektiven study is presented, in which der Zeitpunkt der Weheninduktion hinsichtlich postpartaler maternaler and kindlicher Infektion analysiert.
Abstract: Einleitung Aszendierende Infektionen stellen mögliche Komplikationen nach vorzeitigem Blasensprung (PROM) dar. Die aktuelle Leitlinie [1] empfiehlt daher bei einem PROM ≥37+0SSW die Geburtseinleitung spätestens nach 24 Stunden. Die kürzlich publizierte Sekundäranalyse der TERMPROM-Studie kam zu dem Schluss, dass eine frühere Einleitung unmittelbar nach PROM vorteilhaft ist [2]. In dieser retrospektiven Studie wird der Zeitpunkt der Weheninduktion hinsichtlich postpartaler maternaler und kindlicher Infektion analysiert.